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EC number: 486-070-7 | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 28 October 2009 to 20 July 2011
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: The study was performed according to international test guidelines and to GLP.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
- Reference Type:
- other: First amendment to report
- Title:
- Unnamed
- Year:
- 2 010
- Report date:
- 2010
- Reference Type:
- other: Second amendment to report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3465 (90-Day Inhalation Toxicity)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Test material form:
- other: liquid
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories, B.V., Kreuzelweg 53, 5961 NM Horst / Netherlands.
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: males: 291.7 to 337.7 g ; females: 181.4 to 209.1 g
- Fasting period before study: no
- Housing: In groups of five in Makrolon type-4 cages with wire mesh tops and sterilized standard softwood bedding (‘Lignocel’ J. Rettenmaier & Söhne GmbH & Co. KG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland).
- Diet: Pelleted standard Kliba Nafag 3433 (batch nos. 35/09 and 87/09) rodent maintenance diet (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) was available ad libitum except for the periods when the animals were restrained in the exposure tubes and prior to blood sampling for clinical laboratory investigations.
- Water: Community tap-water from Füllinsdorf was available ad libitum in water bottles except for the periods when the animals were restrained in the exposure tubes.
- Acclimation period: 13 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 with music during the light period.
IN-LIFE DATES: From 11 November 2009 to 11 February 2010
Administration / exposure
- Route of administration:
- inhalation: aerosol
- Type of inhalation exposure:
- nose only
- Vehicle:
- air
- Remarks on MMAD:
- MMAD / GSD: Mass Median Aerodynamic Diameters and Geometric Standard Deviations were calculated on the basis of the results from the impactor, using Microsoft Excel Software.
The mean MMAD was below 3 μm (target range was 1 to 3 µm) and therefore the aerosol was considered to be respirable for rats (see summary table below) . In addition, the test item atmosphere of groups 2 and 3 was respirable as the test item was vaporous. - Details on inhalation exposure:
- GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus:Inhalation exposure was performed using a system similar to that originally described by Sachsse et al.
- Method of holding animals in test chamber: The animals were confined separately in restraint tubes which were positioned radially around the flow-past, nose-only exposure chamber as described by Cannon et al.. The design of this chamber is based upon the fluid dynamic modeling of the test aerosol flow.
- Source and rate of air: The exposure system ensured a uniform distribution and provided a constant flow of test material to each exposure tube. The flow of air at each tube was 1.0 L/min, which is sufficient to minimize re-breathing of the test atmosphere as it is more than twice the respiratory minute volume of a rat.
- System of generating particulates/aerosols:The test aerosol was generated using a Hudson nebulizer connected to a syringe pump. The polyethylene injector inside model was replaced by a stainless steel injector. Aerosol concentrations for groups 2 and 3 were achieved by serial dilution of the aerosol generated for exposure of group 4 with compressed, filtered, dry air using an air vacuum device.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity of the test atmosphere was measured continuously and recorded hourly during each exposure using a calibrated device (Rotronic Probe Serie I-200, Rotronic AG).
- Air flow rate: The airflow rate was adjusted before the start of the exposure using a calibrated flow-meter (TSI 4000 series). The actual airflow rate through the exposure chamber was checked hourly during each exposure.
- Method of particle size determination:The cumulative particle size distribution of the test aerosol was determined using a 7 stage cascade Mercer Impactor (Model 02-130, In-Tox. Products Inc., Albuquerque, New Mexico, U.S.A.). The test aerosol was impacted at each stage onto stainless steel slips and the particle size distribution was measured by gravimetrically analyzing the test item deposited on each stage of the cascade impactor. In addition the particle size distribution was determined by chemically analyzing the test item deposited on each stage of the cascade impactor. Immediately after
weighing the steel slip of each stage was put into an appropriately labeled vial and covered with an appropriate amount of Acetonitril. The samples were analyzed using a GC method.
TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determinations of aerosol concentration were performed once per exposure for groups 2 and 3 and three times per exposure for group 4. The test atmosphere samples were collected on a Millipore®durapore filter, Type HVLP, loaded in a 47 mm in-line stainless steel filter sampling device. The filters were weighed before and immediately after sampling using a calibrated balance. The test aerosol concentration was calculated from the amount of test item present on the filter and the sample volume.
- Samples taken from breathing zone: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The analytical phase was conducted at Harlan Laboratories Ltd., Zelgliweg 1, 4452 Itingen, Switzerland under GLP-compliant conditions.
Chemical determinations of aerosol concentration were performed twice per week for groups 2 to 4.
The samples were collected on a Millipore®durapore filter, Type HVLP filter loaded in a stainless steel filter device and in a solvent trap mounted after the filter (groups 2 and 3 only). The solvent trap contained an appropriate amount of Acetonitril and was cooled in an ice/water and covered with 5 mL of Acetonitril.
The samples were analyzed using a GC method. The results were corrected for purity.
The chemical aerosol concentrations were as targeted and stable during the whole treatment period (see summary table below). - Duration of treatment / exposure:
- 13 weeks
- Frequency of treatment:
- 6 hours/day, 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0.01, 0.04, 5 mg/L air
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10 animals/sex/dose
- Control animals:
- yes, concurrent no treatment
- Details on study design:
- Dose selection rationale:
Target aerosol concentrations were selected by the Sponsor based on the results from the previous 2- week inhalation study performed at Harlan Laboratories (study C51304, non-GLP) and information on related substances.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily during treatment and once daily during acclimatization for mortality/viability ; once daily during treatment and once weekly during acclimatization for clinical signs
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: once weekly (each individual animal) during acclimatization and twice weekly during treatment.
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/day: Yes
- Time schedule for examinations: once weekly (per cage) during acclimatization and at least once weekly (per cage) during treatment.
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations and dose groups that were examined: At acclimatization (all animals) and at week 13 (control and high dose animals), using a direct ophthalmoscope.
CLINICAL LABORATORY INVESTIGATIONS:
Blood and urine sampling was performed after 13 weeks of treatment for all animals.
Blood samples were drawn from the retro-orbital plexus from all animals under light isoflurane anesthesia. The animals were fasted in metabolism cages for approximately 18 hours before blood sampling but allowed access to water ad libitum. The samples were collected early in the working day to reduce biological variation caused by circadian rhythms.
HEMATOLOGY: Yes
The following haematology parameters were determined: Erythrocyte count, Haemoglobin, Haematocrit, Mean corpuscular volume, Red cell volume distribution width, Mean corpuscular haemoglobin , Mean corpuscular haemoglobin concentration, Haemoglobin concentration distribution width, Reticulocyte count, Reticulocyte maturity index (low, medium, high fluorescence), Platelet count, Total leukocyte count, Differential leukocyte count (Neutrophils, Eosinophils, Basophils, Lymphocytes, Monocytes, Large unstained cells).
Coagulation: Thromboplastin time, Activated partial thromboplastin time.
CLINICAL CHEMISTRY: Yes
The following parameters were determined: Glucose, Urea, Creatinine, total Bilirubin , total Cholesterol, Triglycerides, Phospholipids, Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, Gamma-glutamyl-transferase, Creatine kinase, Sodium, Potassium, Chloride, Calcium, Phosphorus, total Protein, Albumin, Globulin, Albumin/Globulin ratio.
URINALYSIS: Yes
The following parameters were determined: Urine volume (18 hours), Specific gravity (relative density), Color, Appearance, pH value, Nitrite, Protein, Glucose, Ketones, Urobilinogen, Bilirubin, Erythrocytes, Leukocytes. - Sacrifice and pathology:
- SACRIFICE:
All animals were sacrificed after 13 weeks of treatment. They were anesthetized by intraperitoneal injection of pentobarbitone and killed by exsanguination. All animals were weighed and necropsied. Descriptions of all macroscopical abnormalities were recorded.
ORGAN WEIGHTS:
The following organs were weighed before fixation and recorded on the scheduled dates of necropsy: Adrenal glands, Brain (including section of medulla/pons, cerebral and cerebellar cortex), Epididymides, Heart including auricles, Kidneys, Liver, Lungs, Ovaries, Spleen, Testes, Thymus, Thyroid incl. parathyroid gland and Uterus with vagina. Relative organ weights were calculated on the basis of the body weight and brain weight.
GROSS PATHOLOGY: Yes
Samples of the following tissues and organs were collected from all animals at necropsy and fixed in neutral phosphate buffered 4% formaldehyde solution except for eyes with optic nerve which were fixed in Davidson's solution or epididymides and testes which were fixed in Bouin’s solution: Adrenal glands,Aorta,Bone (sternum, femur including articular surface), Bone marrow (femur), Brain (including section of medulla/pons, cerebral and cerebellar cortex), Epididymides (fixed in Bouin's solution), Esophagus, Eyes with optic nerve (fixed in Davidson's solution), Heart including auricles, Kidneys, Large intestine (cecum, colon, rectum), Larynx, Lacrimal gland (exorbital), Liver, Lungs (filled via trachea with formalin at approximately 30 cm H2O pressure), Lymph nodes (mesenteric, mandibular and mediastinal), Mammary gland area (females only), Nasal cavity, Nasopharyngeal duct and pharynx, Olfactorial bulb, Ovaries, Pancreas,
Peyers Patches, Pituitary gland, Prostate gland including coagulating glands, Salivary glands (mandibular, sublingual), Sciatic nerve, Seminal vesicles, Skeletal muscle, Skin and subcutaneous tissue, Small intestine (duodenum, jejunum, ileum), Spinal cord (cervical, midthoracic, lumbar segments), Spleen, Stomach, Teeth, Testes (fixed in Bouin's solution), Thymus, Thyroid incl. parathyroid gland, Tongue, Trachea (adjacent to larynx and carina and bifurcation), Urinary bladder (filled with formalin at necropsy), Uterus with vagina, All gross lesions)
HISTOPATHOLOGY: Yes
All organs and tissues (except for the Peyers Patches and tongue) which were collected at scheduled sacrifices from all animals of the control and high-dose groups and all gross lesions from all animals were processed, embedded and cut at an approximate thickness of 2 to 4 micrometers and stained with hematoxylin and eosin. The slides were then examined by the study pathologist. As test item-related changes were recorded in organs of the high dose group, these organs from the mid and low dose group were examined as well. - Statistics:
- The following statistical methods were used to analyze food consumption, body weight, opthalmoscopic findings, clinical laboratory data, organ weights and ratios as well as macroscopic findings:
• The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied if the variables could be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
• The Steel-test (many-one rank test) was applied instead of the Dunnett-test when the data could not be assumed to follow a normal distribution.
• Fisher's exact-test.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, treatment-related
- Mortality:
- mortality observed, treatment-related
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Urinalysis findings:
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Details on results:
- CLINICAL SIGNS AND MORTALITY:
All animals survived the scheduled treatment period.
Salivation was recorded in all males and females during most of the treatment period at 5 mg/L air. Breathing noise was recorded in one male of this group during the last five days of treatment.
BODY WEIGHT AND WEIGHT GAIN:
Body weight loss was recorded in males and females during the first four days of exposure at 5 mg/L air. Slight body weight loss or stagnation in body weight was also recorded in the other groups treated with the test item, but also in females of the control group.
Statistically significantly decreased body weight gain and absolute body weight was observed in males and females exposed at 5 mg/L air during the whole treatment period. Lower body weight compared to control animals was also recorded in animals at 0.01 mg/L air during several weeks.
FOOD CONSUMPTION:
Statistically significantly decreased food consumption was recorded in males (-15.4% below the control group) at 5 mg/L air during most of the treatment period and in females (-9% compared to controls) at this aerosol concentration during the first week.
OPHTHALMOSCOPIC EXAMINATION:
There were no ophthalmic changes that were considered to be related to treatment with the test item.
HAEMATOLOGY:
There were no changes in hematology parameters that were considered to be related to treatment with the test item.
CLINICAL CHEMISTRY:
Statistically significant increase in urea, sodium and chloride values was observed in males exposed at 5 mg/L air. These values were also increased in females at this aerosol concentration with statistical significance of sodium only.
Statistically significant increase in sodium and chloride was also observed in males treated at 0.04 mg/L air. There was no dose-dependence pattern observed in females for urea, sodium and chloride increase.
URINALYSIS:
In males treated with the test item the following group mean values were modified: decreased urine volume (with statistical significance in groups 3 and 4 only) as well as increased relative density (statistically significant in all groups) and protein values (with statistical significance in groups 2 and 4). These values were also modified in females (statistical significance for protein values only) at 5 mg/L air. Statistically significantly decreased pH was recorded in males at 5 mg/L air.
ORGAN WEIGHTS:
Statistically significant increase in relative weights of adrenals and kidneys were recorded in males and females after exposure at 5 mg/L air. Absolute adrenal weight was statistically significantly increased in females at 5 mg/L air. Statistically significant increase in lung weight ratios and decrease in thymus/brain weight ratio was observed in males of this group.
GROSS PATHOLOGY:
There were no macroscopic findings that were considered to be related to treatment with the test item.
HISTOPATHOLOGY (NON-NEOPLASTIC):
Minimal epithelial atrophy in the trachea was recorded in some animals exposed at 5 mg/L air.
Squamous metaplasia of the respiratory epithelium, inflammatory exudates, necrosis of the epithelium, inflammation of the submucosa, respiratory metaplasia of the olfactory epithelium and ulceration was recorded in the nasal cavity of some animals at 5 mg/L air with minimal to moderate intensity.
Slightly increased severity of thymus atrophy / involution was recorded in a few animals treated at 5 mg/L air.
Degeneration / regeneration of the respiratory or olfactory epithelium was observed at section levels 1 to 4 of the nasal cavity with a minimal to moderate intensity in most of the animals at 5 mg/L air, and marked effects in one male at section Level 2.
Four females at 0.04 mg/L air had minimal (2 females) to slight (2 females) effects, at level 3 of the nasal cavity (olfactory epithelium).
In the group treated at 0.01 mg/L air, degeneration / regeneration of the olfactory epithelium of minimal intensity was recorded in 3 males (sections levels 3 or 4) , and with slight intensity in 1 female (at Level 3).
Incidence and mean severity of degeneration / regeneration of the respiratory or olfactory epithelium are summarized in the table below.
Effect levels
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 0.04 mg/L air (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on the microscopic findings in the respiratory tract, especially in the nasal cavities (degeneration/regeneration of the respiratory or olfactory epithelium), observed at the high dose of 5.0 mg/L air.
- Remarks on result:
- not measured/tested
- Remarks:
- Effect level not specified (migrated information)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Incidence and mean severity of degeneration / regeneration of the respiratory or olfactory epithelium:
Finding |
Group 1 |
Group 2 |
Group 3 |
Group 4 |
||||
Incidence / Mean Severity |
10 M |
10 F |
10 M |
10 F |
10 M |
10 F |
10 M |
10 F |
Nasal Cavity, Level 1 Degener. / Regener. |
- |
- |
- |
- |
- |
- |
8/1.9 |
6/1.3 |
Nasal Cavity, Level 2 Degener. / Regener. |
- |
- |
- |
- |
- |
- |
10/2.7 |
9/2.3 |
Nasal Cavity, Level 3 Degener. / Regener. |
- |
- |
2/1.0 |
1/2.0 |
- |
4/1.5 |
9/2.1 |
9/1.9 |
Nasal Cavity, Level 4 Degener. / Regener. |
- |
- |
1/1.0 |
- |
- |
- |
8/2.0 |
7/1.7 |
The severity is expressed as the mean of the individual grading (1: minimal, 2: slight, 3: moderate, 4: marked).
Applicant's summary and conclusion
- Conclusions:
- Based on the microscopic findings in the respiratory tract, especially in the nasal cavities (degeneration/regeneration of the respiratory or olfactory epithelium), observed at the high dose of 5.0 mg/L air, the overall no-observed-adverse-effect-concentration (NOAEC) of Dimethyl 2-Methylglutarate for this study was established at 0.04 mg/L air.
For systemic effects the NOAEC was considered to be 5 mg/L air. - Executive summary:
In this study, Dimethyl 2-Methylglutarate was administered to rats by nose-only inhalation for 6 hours a day for a period of 13 weeks.
The study comprised four groups containing ten male and ten female rats each. The animals of the control group (group 1) were exposed to air only. The following aerosol concentrations were administered:
Group 1: 0 mg/L air
Group 2: 0.01 mg/L air
Group 3: 0.04 mg/L air
Group 4: 5.0 mg/L air
Throughout the study all animals were observed for viability and clinical signs. In addition body weights and food consumption were recorded. Ophthalmoscopic examinations were performed and blood and urine samples were taken for clinical laboratory investigations. Following completion of the treatment period, a detailed necropsy was performed on all animals and selected organs were weighed. Various tissues and organs were placed in fixative, processed and examined microscopically.
The achieved chemical aerosol concentrations were between 100 and 112 % of the target. Temperature, relative humidity and oxygen concentration in the inhalation chamber were considered to be satisfactory for this study type.
The particle size distribution was determined for group 4 only as part of the atmosphere of group 2 and 3 was vaporous. The chemical mean mass median aerodynamic diameter (MMAD) was 2.50 μm and the mean geometric standard deviation (GSD) was 2.90. Therefore the aerosol of all groups was considered to be respirable for rats.
All animals survived the scheduled treatment period. Salivation was recorded in all animals at 5 mg/L air. Breathing noise was recorded in one male of this group during the last five days of treatment.
Reduced food consumption associated with a decreased body weight gain was recorded in animals exposed at 5.0 mg/L air.
Increase in urea, sodium and chloride values was observed in animals exposed at 5 mg/L air.
In males treated with the test item the following group mean values were statistically significantly modified: decreased urine volume (groups 3 and 4 only) as well as increased relative density and protein values (groups 2 and 4 only). These values were also modified in females at 5 mg/L air. Statistically significantly decreased pH was recorded in males at 5 mg/L air.
There were no ophthalmic changes and no changes in hematology that were considered to be related to treatment with the test item.
Increase in relative weights of the kidneys were recorded in males and females after exposure at 5 mg/L air. Increase in lung/body weight ratio was observed in males of this group.
There were no macroscopic findings that were considered to be related to treatment with the test item.
The following microscopic changes were recorded:
- Epithelial atrophy in the trachea of animals at 5 mg/L air.
- Squamous metaplasia of the respiratory epithelium, inflammatory exudates, necrosis of the epithelium, inflammation of the submucosa, respiratory metaplasia of the olfactory epithelium and ulceration in the nasal cavity of animals at 5 mg/L air.
- Degeneration / regeneration of the respiratory or olfactory epithelium in the nasal cavity (nasal section levels 1 to 4) of minimal to marked intensity in animals treated at 5 mg/L. Minimal effects on the olfactory epithelium (lower severity and lower incidence) were observed in the lower dose groups. However, the effects observed at 0.01 and 0.04 mg/L air are considered to be unspecific since similar variations were observed in some control animals of the preliminary Dose range finding study (2 -week repeated dose study) as well as in Harlan Laboratories Ltd historical control data.
For systemic effects the NOAEC was considered to be 5 mg/L air.
This 13 -week inhalation toxicity study in the rat is classified acceptable and satisfies the guideline requirement for a subchronic (90 days) inhalation study OECD413 in rats.
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